Amentoflavone from Selaginella tamariscina inhibits SARS-CoV-2 RNA-dependent RNA polymerase

The SARS-CoV-2 pandemic caused millions of deaths due to its prominent infectivity and mortality. Although the vaccines and medicines for SARS-CoV-2 are on the market, new coronavirus variants like influenza are expected to reemerge continuously. Therefore, effective and inexpensive medicines will be required to respond to SARS-CoV-2 variants. Here, we used herbal plant extracts to search for effective compounds that can interfere with SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and found that Selaginella tamariscina extract (STE) can reduce SARS-CoV-2 RdRp activity. The HCoV-OC43 beta coronavirus model was used to examine whether STE treatment could inhibit coronavirus replication and reduce coronavirus-induced cytotoxicity. Next, we searched the active compound of STE and found that amentoflavone is the main active compound of STE. Finally, we demonstrated that amentoflavone inhibits SARS-CoV-2 RdRp and coronavirus replication. Our results collectively indicate that amentoflavone from STE is possibly beneficial in responding to coronavirus-related diseases, including SARS-CoV-2.